Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

Ryan O. Walters, Esperanza Arias-Perez, Antonio Diaz, Emmanuel S. Burgos, Fangxia Guan, Simoni Tiano, Kai Mao, Cara L. Green, Yunping Qiu, Hardik Shah, Donghai Wang, Adam D. Hudgins, Tahmineh Tabrizian, Valeria Tosti, David Shechter, Luigi Fontana, Irwin J. Kurland, Nir Barzilai, Ana Maria Cuervo, Daniel E.L. Promislow & 1 others Derek M. Huffman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network. Finally, we show that sarcosine can activate autophagy in cultured cells and enhances autophagic flux in vivo, suggesting a potential role in autophagy induction by DR. Thus, these data identify circulating sarcosine as a biomarker of aging and DR in mammalians and may contribute to age-related alterations in the metabolome and in proteostasis. In a comparative metabolic screen of rodents and humans, Walters et al. show that circulating sarcosine is similarly reduced with aging and increased by dietary restriction. They demonstrate that sarcosine activates macroautophagy in cultured cells and in vivo, suggesting a role in improved proteostasis via dietary restriction.

Original languageEnglish (US)
Pages (from-to)663-676.e6
JournalCell Reports
Volume25
Issue number3
DOIs
StatePublished - Oct 16 2018

Fingerprint

Sarcosine
Rodentia
Aging of materials
Metabolome
Autophagy
Rats
Cultured Cells
Cells
Biogenic Amines
Metabolomics
Biomarkers
Modulators
Homeostasis
Tissue
Fluxes
Plasmas

Keywords

  • aging
  • amino acids
  • autophagy
  • dietary restriction
  • glycerophospholipids
  • glycine
  • GNMT
  • metabolomics
  • methionine
  • sarcosine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans. / Walters, Ryan O.; Arias-Perez, Esperanza; Diaz, Antonio; Burgos, Emmanuel S.; Guan, Fangxia; Tiano, Simoni; Mao, Kai; Green, Cara L.; Qiu, Yunping; Shah, Hardik; Wang, Donghai; Hudgins, Adam D.; Tabrizian, Tahmineh; Tosti, Valeria; Shechter, David; Fontana, Luigi; Kurland, Irwin J.; Barzilai, Nir; Cuervo, Ana Maria; Promislow, Daniel E.L.; Huffman, Derek M.

In: Cell Reports, Vol. 25, No. 3, 16.10.2018, p. 663-676.e6.

Research output: Contribution to journalArticle

Walters, Ryan O. ; Arias-Perez, Esperanza ; Diaz, Antonio ; Burgos, Emmanuel S. ; Guan, Fangxia ; Tiano, Simoni ; Mao, Kai ; Green, Cara L. ; Qiu, Yunping ; Shah, Hardik ; Wang, Donghai ; Hudgins, Adam D. ; Tabrizian, Tahmineh ; Tosti, Valeria ; Shechter, David ; Fontana, Luigi ; Kurland, Irwin J. ; Barzilai, Nir ; Cuervo, Ana Maria ; Promislow, Daniel E.L. ; Huffman, Derek M. / Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans. In: Cell Reports. 2018 ; Vol. 25, No. 3. pp. 663-676.e6.
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AU - Guan, Fangxia

AU - Tiano, Simoni

AU - Mao, Kai

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